肥胖特征肠菌的跨疾病调控机制及诊疗新策略

Obesity-associated gut microbiota: cross-disease regulatory mechanisms and novel diagnostic/therapeutic strategies

摘要:

肥胖及其相关代谢性疾病的全球发病率持续上升，已成为重大公共卫生问题。肠道菌群在肥胖的发生发展过程中扮演着关键角色，其组成和功能紊乱与肥胖及其相关并发症直接相关。本文综述了肥胖的遗传、神经内分泌、慢性炎症以及肠道菌群代谢轴等病理机制，重点梳理了脱硫弧菌、巨单胞菌等条件致病菌和乳酸杆菌、嗜黏蛋白阿克曼氏菌等益生菌对肥胖的正、负调控机制，总结了肥胖特征性肠菌在糖尿病、代谢功能障碍相关脂肪性肝病、心血管疾病和高血压发生中的驱动机制，创新性地提出了肥胖疾病的肠菌演变假说，并展望了未来肥胖特征性肠菌的研究趋势以及疾病早期诊断技术的开发前景。本文将为肥胖及相关代谢性疾病的早期诊断和精准干预提供新策略，有助于推动个性化诊疗的发展。

Abstract:

The global prevalence of obesity and its associated metabolic disorders keeps rising, presenting a major challenge to public health. The gut microbiota plays a pivotal role in obesity onset and development, and its dysbiosis and dysfunction are closely associated with obesity and its complications. This review synthesizes the pathological mechanisms underlying the heredity, neuroendocrine, chronic inflammation, and the gut microbiota-metabolism axis of obesity. Then, we explore the positive and negative regulatory effects of opportunistic pathogens (e.g., Desulfovibrio spp., Megamonas spp.) and putative beneficial bacteria (e.g., Lactobacillus spp., Akkermansia muciniphila) on obesity. Furthermore, we summarize the mechanisms by which these signature gut microbes drive the development of obesity-related conditions, including type 2 diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, cardiovascular diseases, and hypertension. We firstly propose a gut microbiota trajectory hypothesis to delineate the interrelationships between these representative gut microbial signatures and the onset and progression of obesity and its complications. Finally, the review discusses future research directions and the potential for developing early diagnostic technologies based on these microbial signatures. Collectively, this work aims to provide novel strategies for the early diagnosis and precision intervention of obesity and related metabolic disorders, thereby advancing the development of personalized therapeutics.